No evidence for leptin as an independent associate of blood pressure in childhood and juvenile obesity

We studied whether leptin is an independent associate of blood pressure in obese children and adolescence. 102 obese children (48 girls, age: 11.6 +/- 2.22 yr; body mass index [BMI]: 27.45 +/- 4.4; blood pressure: 122.5 +/- 11.1/64.7 +/- 10.6 mm Hg and 54 boys, age: 11.5 +/- 2.4 yr; BMI: 27.6 +/- 4.4; blood pressure: 122.5 +/- 13.2/60.9 +/- 8.1 mm Hg [mean +/- SD]) were investigated. Serum leptin and insulin were measured by RIA; glucose was determined enzymatically. Fat mass (FM) was calculated by bioelectrical impedance. Leptin was higher in girls than in boys (p=0.018) but no significant gender differences were found with respect to indices of adiposity and systolic blood pressure (SBP). Children were divided into three groups, according to pubertal stage (Group 1: prepubertal, 32 boys/13 girls; Group 2: pubertal, 17 boys/25 girls; Group 3: late/postpubertal, 5 boys/10 girls). SBP and DBP correlated with body weight in the whole group (r=0.49, p<0.0001, and r=0.27, p=0.004). In Group 1, BMI showed the highest correlation to SBP; in Group 3 no indices of adiposity were related to SBP. In no case was leptin significantly associated with SBP after adjustment for adiposity. In Group 2, glucose was significantly associated with SBP after adjustment for body weight. In Group 3, however, no correlations were found between SBP, DBP and metabolic characteristics, perhaps due to small sample size. Stepwise multiple regression revealed that body weight and glucose contributed to the variation in SBP in the whole group (R2=0.31, p<0.0001). Insulin accounted for almost 8% of the variation in DBP (R2=0.08, p=0.0034). Body weight contributed significantly to SBP in boys (R2=0.39, p<0.0001) and girls (R2=0.24, p< 0.001). The results imply that body weight contributes independently to the variation in blood pressure. Glucose and insulin contribute to mean blood pressure to some extent, but our data do not support the assumption that leptin per se serves as an independent predictor of blood pressure in obese children and adolescents.     

Insulin resistance of puberty in African-American children: lack of a compensatory increase in insulin secretion

Type 2 diabetes has been increasing in children, mostly affecting minority populations at around the age of puberty. Despite a multitude of studies demonstrating pubertal insulin resistance/hyperinsulinemia in white children, data are almost non-existent in African-American children. The aim of the present study was to investigate the impact of puberty on glucose metabolism, insulin sensitivity and secretion in African-American children. Twenty prepubertal and 16 pubertal African-American subjects participated. All underwent a 3-h hyperinsulinemic (40 mU/m(2)/min) euglycemic clamp to determine insulin-stimulated glucose disposal, and a 2-h hyperglycemic (12.5 mmol/L) clamp to assess first- and second-phase insulin secretion. Body composition was assessed by dual energy X-ray absorptiometry (DEXA) and visceral and subcutaneous abdominal adiposity with computed tomography (CT) scan at L4-L5. Total glucose disposal, glucose oxidation and non-oxidative glucose disposal were significantly lower in the pubertal group compared with the prepubertal one (53.8 +/- 3.9 vs. 72.2 +/- 5.0 micromol/kg/min, p = 0.009; 23.3 +/- 1.1 vs. 31.6 +/- 1.7 micromol/kg/min, p = 0.001; and 30.0 +/- 3.3 vs. 40.5 +/- 3.9 micromol/kg/min, p = 0.049, respectively). Insulin sensitivity was approximately 30% lower in the adolescents compared with the prepubertal children. However, first- and second-phase insulin secretions were not different between the two groups (971.4 +/- 180.6 vs. 1044.0 +/- 191.4 pmol/L and 999.6 +/- 159.6 vs. 955.8 +/- 142.2 pmol/L, respectively). In conclusion, despite approximately 30% lower insulin sensitivity in African-American adolescents compared with prepubertal children, insulin secretion is not higher. This is in contrast to published findings in white children in whom insulin secretion is higher during puberty. These racial differences in physiologic adaptation to puberty could play a role in the higher prevalence of type 2 diabetes in African-American children at the time of puberty.     

Relationship between plasma leptin, insulin and tumor necrosis factor alpha in obese children

OBJECTIVES: 1. To evaluate the relationship between plasma leptin and TNFalpha concentrations in obese children and to assess the differences between hyperinsulinemic and normoinsulinemic groups. 2. To evaluate the relationship between plasma leptin and insulin levels in obese children. 3. To investigate the TNFalpha G308A mutation in obese children. METHODS: Body mass index (BMI), fasting plasma glucose and insulin levels, oral glucose tolerance test results, homeostasis model assessment of insulin resistance (HOMA-IR) results, and plasma leptin and TNFalpha concentrations were evaluated in obese children (n = 45) and age- and gender-matched, lean healthy controls (n = 40). RESULTS: In obese children the fasting insulin, HOMA-IR results, plasma leptin and TNFalpha concentrations were significantly higher than in controls (p <0.05). Furthermore, obese females showed higher plasma leptin and insulin resistance compared to obese males. While plasma leptin, TNFalpha levels and HOMA-IR results were similar in the prepubertal and pubertal groups, insulin levels were significantly higher in the pubertal group. Plasma leptin and TNFalpha concentrations were similar in hyperinsulinemic and normoinsulinemic obese children. In control children, plasma leptin concentrations showed a positive correlation with BMI, age, fasting insulin and HOMA-IR results. In obese children, plasma leptin levels did not correlate with BMI, fasting insulin or TNFalpha. CONCLUSION: Plasma leptin concentrations did not show any correlation with TNFalpha levels in obese children. Furthermore, plasma leptin and TNFalpha concentrations were similar in hyperinsulinemic and normoinsulinemic obese children.     

The role of diabetes duration, pubertal development and metabolic control in growth in children with type 1 diabetes mellitus

OBJECTIVE: To investigate whether pubertal development, duration of type 1 diabetes mellitus (DM1), or metabolic control play some role in the anomalies in growth observed in diabetic children. PATIENTS: We conducted a prospective evaluation of 83 patients (37 female, 46 male) who were followed from the onset of DM1 at the prepubertal stage until they reached final height. All patients were treated with a conventional regimen of insulin. METHODS: Height SDS, weight SDS, BMI SDS, duration of DM1 in years, and values of HbA1c were the study variables. RESULTS: In prepubertal (P1) girls (data for the initial vs the intermediate evaluations): weight SDS was -0.14 +/- 0.19 vs 0.11 +/- 0.20, p = ns; BMI SDS -0.25 +/- 0.15 vs 0.01 +/- 0.13, p = ns. In postpubertal (P3) girls, weight SDS was 0.49 +/- 0.2 vs 1.2 +/- 0.32, p <0.01; BMI SDS 0.09 +/- 0.16 vs 1.03 +/- 0.24, p <0.01, whereas in P1 boys, height SDS was 0.16 +/- 0.30 vs -0.20 +/- 0.27, p <0.05; and in P3 boys: 0.09 +/- 0.21 vs -0.28 +/- 0.26, p <0.05. Thus pubertal development influenced changes observed in girls with DM1, but did not do so in boys. The anomalies described in children with DM1 were observed from the third year of DM1 duration in both girls and boys. We did not observe any correlation between HbA1c values with height SDS, weight SDS or BMI SDS. CONCLUSIONS: The anomalies in growth observed in girls with DM1 are related to pubertal development, but this is not the case in boys. Alterations in children with DM1 were found from the third year of DM1 duration. Furthermore, the present data also indicate that the degree of metabolic control observed in our patients treated with modern but conventional regimen did not play a major role in the anomalies observed.     

Long-term suppression of weight gain,adiposity, and serum insulin by central leptin gene therapy in prepubertal rats: effects on serum ghrelin and appetite-regulating genes

Intracerebroventricular administration of recombinant adeno-associated virus (rAAV) encoding the rat leptin gene (rAAV-lep) to 24-d-old female and male rats suppressed postpubertal weight gain for extended periods by decreasing food consumption and adiposity, as reflected by lowered serum leptin, insulin, and FFA. Serum ghrelin levels were increased in young but not older rats. Central rAAV-lep therapy also increased energy expenditure through nonshivering thermogenesis in younger rats as shown by expression of uncoupling protein mRNA in brown adipose tissue. The sustained decrease in appetite seemingly resulted from attenuation of appetite-stimulating neuropeptide Y and enhancement of appetite-inhibiting melanocortin signalings in the hypothalamus. Neither the onset of pubertal sexual maturation nor reproductive cyclicity in adult female rats was affected by the sustained reduction in energy consumption and weight gain. These findings demonstrate that central leptin gene therapy in prepubertal rats is a novel therapy to control postpubertal weight gain, adiposity, and hyperinsulinemia for extended periods.     

Insulin and insulin resistance index are not independent determinants for the variation in leptin in obese children and adolescents

Recent findings have questioned the independent influence of insulin on leptin. We studied whether insulin contributes to leptin in obese children, independent of confounding parameters, such as total adiposity, fasting insulin resistance index, and fat free mass. In 100 obese boys and 103 obese girls, blood levels of leptin, insulin, glucose, and triglycerides were determined. The fasting insulin resistance index (FIRI) was calculated, and body composition was assessed by means of impedance. Leptin and glucose were higher in girls, and all estimates of adiposity were significantly associated with leptin. However, when adjusted for adiposity, the relationship between insulin and leptin, and also between FIRI and leptin, remained significant in boys and girls (p<0.05). Although several regression models were tested, neither insulin nor FIRI were found to contribute significantly and independently to leptin. BMI together with triglycerides and FFM were the main determinants for the variation in leptin in boys (adj. R2=0.46, p<0.0001). In girls, BMI explained a great magnitude of the variation in leptin (adj. R2=0.60, p<0.0001). These findings indicate that in the state of childhood and adolescent obesity, total adiposity but not insulin or insulin resistance index is the main determinant for leptin. In contrast to obese girls, the fat free mass and triglycerides contribute significantly to the variation in leptin in obese boys. The biological significance for these findings should be elucidated in longitudinal studies.     

Serum leptin levels in premature pubarche and prepubertal girls with and without obesity

Leptin can be regarded as a marker of the nutritional status of the body. This study was performed to determine the correlation of leptin levels with insulin (I) and androgens in girls with premature pubarche (PP) and prepubertal controls (C) with (OB) or without (nOB) obesity. We studied 25 girls with PP and 14 C; girls were dived into two subgroups according to body mass index (BMI): OB (18 PP and 8 C) and nOB (7 PP and 6 C). Obesity was defined as BMI >95th percentile for chronological age. Serum levels of leptin, I, glucose (G), DHEAS, testosterone, androstenedione (A), cortisol, SHBG, IGFBP-1 and lipid profile were measured. The fasting G to I ratio (FGIR) was calculated and FGIR <7 was considered as suggestive of I resistance (IR). Data were analyzed comparing PP vs C and OB vs nOB. Serum DHEAS (0.60 +/- 0.45 vs 0.18 +/- 0.22 microg/ml) and A (895.5 +/- 420.4 vs 457.0 +/- 352.1 pg/ml) levels were significantly higher in PP than C. Other hormonal and metabolic parameters were similar. Serum leptin (30.8 +/- 18.3 vs 8.1 +/- 5.9 ng/ml), A (841.8 +/- 471.1 vs 522.5 +/- 317.2 pg/ml), DHEAS (0.53 +/- 0.44 vs 0.31 +/- 0.39 microg/ml), G (88.4 +/- 8.8 vs 80.2 +/- 8.1 mg/dl), I (13.5 +/- 7.7 vs 5.1 +/- 3.7 microU/ml) and total cholesterol (TC) (180.5 +/- 30.9 vs 161.8 +/- 29.5 mg/dl) levels were greater in the OB than in the nOB group. IR was observed in 10 girls with OB and in one with nOB. Leptin was correlated with BMI (r = 0.83), SHBG (r = -0.44), IGFBP-1 (r = -0.47), I (r = 0.37), A (r = 0.48) and TC (r = 0.36), but in multiple regression analysis only with BMI (r2 = 0.72, p < 0.001). Girls with PP and prepubertal OB girls showed elevated leptin levels independent of I and androgen levels. Girls with OB had a greater degree of hyperandrogenism and IR. As obesity, IR and hyperandrogenism are common findings in polycystic ovary syndrome (PCOS), which is more prevalent in young women with a history of PP, a role of leptin in PCOS can be suggested. In addition, girls with PP could be considered a population at risk for plurimetabolic syndrome.     

Relationships of IGF-I and andrrogens to skeletal maturation in obese children and adolescents

IGF-I and androgens are postulated to accelerate skeletal maturation in obese children. METHODS: We studied weight status (BMI-SDS), height-SDS, IGF-I, cortisol, DHEA-S, and testosterone in 356 obese children (aged 4-15 years; 54% females) and correlated them to differences between bone age and chronological age (deltaBA-CA). Direct multivariate linear regression analyses were conducted for the dependent variable deltaBA-CA, including BMI, age, gender, pubertal stage, IGF-I-SDS, cortisol, DHEA-S, and testosterone as independent variables separately in prepubertal and pubertal girls, and prepubertal and pubertal boys. RESULTS: Height-SDS (r = 0.52), IGF-I (r = 0.33), and IGF-I-SDS (r = 0.36) were significantly (p < 0.001) correlated to deltaBA-CA. In multiple regression analyses, BMI and IGF-I-SDS were significantly positively (p < 0.001) correlated to deltaBA-CA independently of gender and pubertal stage. Testosterone was significantly positively correlated to detaBA-CA only in prepubertal girls (p = 0.035). CONCLUSIONS: Since IGF-I concentrations were positively associated to deltaBA-CA independently of pubertal stage and gender, we put forward the hypothesis that this hormone may contribute to acceleration of skeletal maturation in obese children.     

Leptin, insulin-like growth factor (IGF)-I and IGF binding protein-3 levels in children with constitutional delay of growth

This study was planned in order to investigate the role of insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3) and leptin, the product of the ob gene synthesized by fat tissue cells, in constitutional delay of growth and puberty (CDGP) which is the most frequent cause of short stature in children. This study was conducted on 80 children with CDGP aged 6-15 years, and 60 healthy children served as controls. Serum IGF-I, IGFBP-3, insulin and plasma leptin levels were measured by immunoradiometric assay. Mean IGF-I and leptin levels were significantly lower in the CDGP group compared with the controls, but the mean IGFBP-3 level was not different in the two groups. Mean leptin levels were 3.72 +/- 2.29 in CDGP and 4.68 +/- 3.08 in the control group (p <0.05). There was a statistically significant relationship between leptin levels and height, weight, and body mass index. Leptin levels were also correlated with chronological age, bone age and height age. When evaluated according to pubertal status, a significant difference was found in IGF-I, leptin and IGFBP-3 levels between prepubertal and pubertal groups. Leptin levels were significantly different in the prepubertal CDGP group compared with controls but in the pubertal CDGP group only IGF-I levels were significantly different from controls. As the weight of children with CDGP was lower than in the control group, it is postulated that the reason for short stature and pubertal delay may be this decrease in weight which is also the cause of low levels of leptin and IGF-I.     

Correlates of adiponectin and the leptin/adiponectin ratio in obese and non-obese children

Adiponectin is an adipocyte secreted protein that has been reported to increase fatty acid oxidation and improve insulin sensitivity. Our aim was to study the relationship between adiponectin and leptin, body fat, insulin and lipoproteins in obese compared to non-obese children matched for age and gender. Adiponectin serum concentrations were significantly lower in the obese compared to the non-obese children (9.1+/-3.7 vs 17.1+/-12.3 microg/ml, p <0.05), in contrast to serum leptin concentrations which were greater in the obese compared to the non-obese subjects (31.8+/-11.1 vs 8.2+/-5.7 ng/ml, p <0.001). When considered as a single group to assess adiponectin concentrations over a spectrum of body size, adiponectin values correlated inversely with body weight (r = -0.33, p <0.05) and BMI (r = -0.35, p <0.05). Adiponectin values correlated directly with HDL-C (r = 0.47, p <0.005), but not with total cholesterol, IGF-I, or leptin binding activity. Since leptin and adiponectin change inversely in relation to BMI, the leptin/adiponectin (L/A) ratio was determined as a potential index relating adiposity to the development of complications of obesity. The L/A ratio was eight-fold greater in the obese compared to the non-obese children, and correlated more strongly with BMI (r = 0.779, p <0.0001) and with HDL-C (r = -0.53, p <0.001), than did adiponectin alone. The L/A ratio also correlated significantly with triceps skinfold thickness (TSF) (r = 0.77, p <0.001) and percent body fat (r = 0.79, p <0.0001) in non-obese children. These data suggest that adiponectin concentrations are already differentially regulated in childhood obesity. The index of increased leptin concentration corrected by reduced adiponectin values (L/A ratio) merits investigation as a marker for morbidities associated with childhood obesity.     

Leptin levels decline steadily during prolonged fasting in lean children

OBJECTIVE: To evaluate the effects of fasting on serum leptin levels in lean children. STUDY DESIGN: Seventeen children, age 7.7 +/- 4.3 years with mean body mass index (BMI) of 16.7 +/- 2.7 kg/m(2), underwent standard diagnostic fasts for suspected hypoglycemia. Blood was sampled at 6-hour intervals for glucose, insulin, C-peptide, leptin, free and total insulin-like growth factor-1, insulin-like growth factor-binding protein-1, growth hormone, cortisol, ketones, and free fatty acids. RESULTS: Subjects fasted 15 to 40 hours, and initial leptin levels were related to BMI and age. Leptin declined by 0.5 ng/mL per each fasting hour (P = .008), using a longitudinal mixed effects model. Leptin dropped significantly from an initial mean +/- SEM during the first 6 hours of 15.9 +/- 5.5 ng/mL to 3.5 +/- 0.9 ng/mL at the end of fasting. Mixed longitudinal effects models demonstrated that leptin was significantly related to insulin over time (P < .0001) as well as C-peptide (P < .0001). Significant relations were also seen with total insulin-like growth factor-1 over time, beta-hydroxybutyrate and insulin, and insulin-like growth factor-binding protein-1 and insulin. CONCLUSIONS: After 6 hours, leptin levels steadily decline during prolonged fasting in lean children. The decline probably is related to the suppression of insulin secretion. Although baseline leptin levels were related to BMI and age, in the final fasting sample, leptin levels showed minimal variation in this pediatric cohort encompassing a wide age range.     

小于胎龄儿青春前期女孩硫化脱氢表雄酮和胰岛素水平的研究

目的探讨小于胎龄儿(SGA)青春前期女孩肾上腺机能初现及是否具有肾上腺机能早现、高肾上腺雄激素血症、高胰岛素血症和胰岛素抵抗现象。方法以符合纳入标准的SGA 39例为研究对象,年龄(7.4±1.7)岁,42例适于胎龄儿(AGA)为对照组,年龄(7.4±1.7)岁。在隔夜空腹12 h后,行身体检查,并抽血检测空腹血糖、胰岛素、硫化脱氢表雄酮(DHEAS)、皮质醇和雌二醇。胰岛素敏感性用空腹血糖与胰岛素乘积的倒数再取自然对数来评价。结果两组中未发现肾上腺机能早现的临床表现,两组间孕母孕龄、年龄、体重指数、空腹血糖、皮质醇、雌二醇和胰岛素敏感性指数差异无统计学意义。SGA组出生体重、研究时的身高和体重均低于AGA组,SGA血清胰岛素和DHEAS水平均高于AGA组(对数转换值:1.076±0.041vs.1.050±0.051,P<0.05;2.637±0.271vs.2.514±0.250,P<0.05)。AGA组DHEAS值在7岁以后出现明显增加,SGA组DHEAS值出现增加的趋势与AGA组比较有所提前。结论AGA女孩肾上腺机能初现的年龄约为7岁,而SGA女孩肾上腺机能初现有始动提前的趋势,青春前期SGA女孩有高肾上腺雄激素血症和胰岛素水平升高的现象,但以胰岛素敏感性指数来评价,尚未发现胰岛素抵抗现象。     

The relation between skeletal maturation and adiposity in African American and Caucasian children.

OBJECTIVE: African American children have earlier pubertal and skeletal maturation and a higher body mass index (BMI) than Caucasian children. We tested the hypothesis that advanced bone age in African American children is accounted for by their greater adiposity. STUDY DESIGN: We studied 252 African American (n = 97) and Caucasian (n = 155) children aged 5 to 12 years. Skeletal age was determined by a radiologist blinded to clinical details. The difference between bone age (BA) and chronological age (CA) (noted as BA - CA) and the ratio of bone age to chronological age (BA/CA) were determined. Analysis of covariance was used to adjust skeletal maturation for the effects of adiposity, as measured by BMI, BMI standard deviation score (BMI SDS), and fat mass by dual energy x-ray absorptiometry (DXA). RESULTS: African American children were significantly heavier than Caucasians (BMI SDS 2.7 +/- 3.4 vs 1.7 +/- 2.4, P <.05). Both BA - CA (0.75 +/- 1.46 vs 0.28 +/- 1.38, P <.05) and BA/CA (1.09 +/- 0.17 vs 1.03 +/- 0.16, P <.05) were significantly greater in African Americans than Caucasians. BA - CA and BA/CA were significantly correlated with lean body mass, BMI, BMI SDS, and DXA fat mass (all r > 0.46, P <.001). Neither BA - CA nor BA/CA of African Americans and Caucasians were significantly different after correction for lean body mass and measures of adiposity, including BMI, BMI SDS, or DXA fat mass. CONCLUSION: Skeletal age is more advanced in African American than Caucasian children and is significantly related to body mass. In large measure, the advancement in skeletal maturation of prepubertal and early pubertal African American children can be accounted for by their greater adiposity.     

Reduced levels of growth hormone, insulin-like growth factor-I and binding protein-3 in patients with shunted hydrocephalus

OBJECTIVE: Children with hydrocephalus are characterised by slow linear growth in prepuberty, accelerated physical maturation during puberty, and reduced final height. We aimed to study the possible roles of growth hormone, insulin-like growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3) in this growth pattern. STUDY DESIGN: One hundred and fourteen patients with shunted hydrocephalus (62 males) aged 5 to 20 years, of whom 17 had spina bifida (six males), and 73 healthy controls (38 males) were studied. Anthropometric measures, body mass index, and body fat mass were assessed and the stage of puberty was determined. Serum growth hormone and plasma IGF-I and IGFBP-3 concentrations were measured. RESULTS: The patients comprised 44 (26 males) who were prepubertal and 70 (36 males) pubertal or postpubertal, while 32 of the controls (19 males) were prepubertal and 41 (19 males) pubertal or postpubertal. The prepubertal children with hydrocephalus had lower IGF-I (p = 0.002) and IGFBP-3 concentrations (p < 0.001) than the controls, and the pubertal children had four times lower basal growth hormone concentrations (p < 0.001). There was a correlation between height SD score and IGF-I levels in the total patient population (r = 0.23; p = 0.01). Peripheral IGF-I concentrations peaked at pubertal stages 2-3 in the female patients and at stage 4 in the controls. The prepubertal patients on antiepileptic treatment, carbamazepine in most cases (73%), had higher IGF-I (p = 0.01) and IGFBP-3 concentrations (p = 0.03) than those who had never been treated with antiepileptic drugs, but still lower IGFBP-3 levels than the controls (p = 0.01). CONCLUSION: Based on these findings, it can be concluded that reduced growth hormone secretion may contribute to the pattern of slow linear growth and reduced final height observed in these patients.     

Serum leptin levels during childhood and adolescence: relationship with age, sex, adiposity and puberty

We studied serum leptin levels in 189 healthy children to evaluate related factors during childhood and adolescence. Leptin correlated with body mass index (BMI), triceps skinfold thickness (p<0.001) and body weight (p<0.01). Obese children and girls had higher leptin levels than non-obese children and boys, respectively (p<0.001). In girls, leptin correlated positively with age, skinfold thickness and BMI (p<0.001). In boys, leptin correlated negatively with age (p<0.001) and positively with skinfold thickness (p<0.05). Prepubertal boys had higher leptin levels than prepubertal girls and pubertal boys (p<0.05). Pubertal girls had higher leptin levels than prepubertal girls and pubertal boys (p<0.001). Leptin levels in girls were higher at Tanner stages 4 and 5 than at stage 1 (p<0.001). In conclusion, serum leptin levels are related with adiposity, have obviously age-related gender differences during childhood and adolescence, and may be involved in the maturation of reproductive capacity.     

The effects of androstenediol and dehydroepiandrosterone on the immune response to BCG at puberty

In order to assess the effects of age-related changes of serum dehydroepiandrosterone sulphate (DHEAS) and androstenediol (AED) concentrations on BCG vaccination throughout the puberty period, we matched 41 prepubertal (mean age 8.63 +/- 1.36 years, range 8-14 years) and 43 pubertal (mean age 13.8 +/- 1.31 years, range 10-16 years) schoolchildren who were PPD negative and free of disease or medication known to affect immune function. The tuberculin test was performed 8 weeks after vaccination and tuberculin response and hormone levels were compared between prepubertal and pubertal subjects. We found a higher tuberculin response in the pubertal group when compared with the prepubertal ones. The pubertal children had 79.1 per cent tuberculin positivity compared with 46.4 per cent of prepubertal children (p < 0.05). Diameters of induration of the tuberculin test among prepubertal students vs. pubertal students were 9.5 +/- 3.8 mm and 11.9 +/- 3.7 mm, respectively (p < 0.005). Pubertal stage, testis volume, and pubic stage were also found to have significant effects on tuberculin test results. No difference was observed between both sexes with regard to responses of the tuberculin test in either the prepubertal or the pubertal group (p > 0.05). DHEAS and AED levels in the tuberculin-positive subjects were found to be significantly higher than tuberculin-negative ones (p = 0.040 and p = 0.046, respectively). Among both these hormones, only AED levels were correlated with tuberculin test responses. These results suggest that AED may play a role in the immunity to BCG vaccination and further immunological investigations are warranted to provide support for this idea.     

Leptin assessment in acute lymphocytic leukemia survivors: role of cranial radiotherapy?

Leptin has been hypothesized to play a role in the development of obesity in leukemia survivors, particularly those who have received cranial radiotherapy. This cross-sectional study evaluated the relationship between leptin levels and body mass index (BMI) in a sample of 26 acute lymphocytic leukemia survivors of both sexes, treated with and without cranial irradiation, aged 7.6 to 17 years, at a mean 3.4+/-2.0 years off treatment. There were significantly more males among the irradiated group (P<0.001), even though no differences were encountered in pubertal stage (P=1.000), BMI standard deviation score (mean+/-SD) (0.68+/-1.00 vs. 1.19+/-0.78; P=0.164), or leptin concentrations (17.01+/-17.04 vs. 23.3+/-13.4; P=0.309). Nonetheless, there was a positive correlation between the natural logarithm of leptin and BMI standard deviation score [t(22)=2.348, P=0.028], however, no differences were recorded among irradiated and nonirradiated patients [F(2,22)=0.384, P=0.685]. When this relationship was compared between sexes, a significant difference was encountered [F(2,22)=4.907, P=0.017], with males having the strongest association (R(2)males=65.5%, R(2)females=34.7%). Leptin is a reliable adiposity index as it strongly correlates with BMI. Overall, the current data suggest that cranial irradiation did not play a role upon this relationship; however, sex differences influenced positively this correlation.     

Pubertal changes in serum leptin levels in adolescents with type 1 diabetes mellitus: a controlled longitudinal study

The mechanism of the pubertal delay seen in some adolescents with type 1 diabetes mellitus is not entirely clear. Since leptin has been implicated as a neuroendocrine modulator of puberty, we measured serum leptin levels longitudinally in 24 post-'honeymoon' patients with diabetes mellitus (M/F = 15/9) with a mean (+/- SD) age of 10.5 +/- 0.9 years and 26 controls (M/F = 15/11) with a mean age of 10.0 +/- 1.1 years. Physical examinations; serum leptin, IGF-I, IGFBP-3 and IGFBP-1 levels; and bone age X-rays were performed annually for up to 48 months. Glycosylated hemoglobin (HbA1c) was measured 2-4 times a year in patients with diabetes mellitus. Serum leptin levels strongly correlated with the body mass index z-scores (BMI-Z) in both controls (r = 0.666, p <0.00001) and diabetic patients (r = 0.577, p <0.00001). Girls had increased serum leptin levels for a given BMI compared to boys (p <0.005). There were no significant differences in serum leptin levels of patients with diabetes mellitus compared to controls, nor were differences seen when the groups were stratified by age, Tanner stage, or gender. There were also no significant correlations between serum leptin levels and degree of metabolic control (i.e. HbA1c) or insulin dose standardized for body weight. Although there was no significant diabetes-related or metabolic control-related delay in bone age z-score or pubertal development, there was a significant negative correlation between HbA1c and growth velocity z-score, indicating that children with poor diabetes control had modest but significant slowing of growth. It is concluded that neither pubertal development nor serum leptin levels are significantly altered in adolescents with diabetes mellitus managed with standard therapy. The potential role of leptin in initiation of pubertal development is not easily demonstrable in observational studies.     

Leptin levels in children with insulin dependent diabetes mellitus

Leptin, a product of the ob gene, is a polypeptide hormone produced in adipose tissue that informs the brain about the amount of energy storage of body fat. It has very important effects on neuroendocrine functions and energy expenditure. The aim of our study was to determine leptin levels of children with insulin dependent diabetes mellitus (IDDM), which is known to affect body metabolism, and to investigate the relationship between duration of the disease, insulin dosage, HbA1c levels, body mass index (BMI), serum lipids and IGF-1 levels. Sixteen patients with IDDM (chronological age 13.8 +/- 2.6 years) whose HbAlc levels were 10.2 +/- 1.9 %, BMI 21.2. +/- 2.7 kg/m2, insulin dosage 0.9 +/- 0.4 U/kg/day and duration of the disease 6.7 +/- 2.6 years, and 12 healthy controls (13.4 +/- 2.6 years) were included in the study. Fasting plasma leptin levels were measured by radioimmunoassay method. The mean plasma leptin levels of the patient and the control groups were 19.1 +/- 7.6 ng/ml and 6.1 +/- 2.9 ng/ml, respectively, and significant difference was found between the two groups (p < 0.05). No correlation was found between leptin values and IGF-1, cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride levels, atherogenic index, insulin dosage or HbA1c levels in the patient group. A weak statistical correlation was determined between BMI and leptin levels in the IDDM group (r = 0.28, p < 0.05). A positive correlation was also found between leptin levels and the duration of the disease (r = 49, p < 0.05). As a result, it seems that leptin levels of children with IDDM differed from the levels of the control group significantly, and that the duration of insulin therapy was responsible for this difference.     

Anthropometric measurements and obesity diagnosis in schoolchildren

Aim: To evaluate whether anthropometric methods such as arm muscle area, arm fat area, Rohrer index, conicity index, and waist‐to‐height ratio and the commonly used body mass index method are suitable for obesity screening in a multiethnic paediatric population. Method: A cross‐sectional population study was carried out in the city of Ouro Preto, Brazil, in 2006. Schoolchildren (n = 788) aged 6–15 years were selected by the stratified random sampling procedure by the proportion of students according to age and gender in all schools. Nonparametric receiver‐operating characteristic analysis was used to define the cut‐off for obesity for each method studied, using the tetrapolar bioelectrical impedance technique as the reference method. Results: Arm fat area measurements and Rohrer index were most suitable for adiposity screening in prepubertal and pubertal boys and in pubertal and prepubertal girls, respectively. In postpubertal period, the Rohrer index was the most suitable body fat assessment method in both genders. Conclusion: Body mass index presented the best balance between sensitivity and specificity only in the prepubertal period and postpubertal boys. Anthropometric measurements, especially arm fat area measurements and Rohrer index, are useful for screening of adiposity in a multiethnic paediatric population.